Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue‐specific regulation for stress‐inducible Hsp molecular chaperones
- 1 January 2002
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 86 (2), 376-393
- https://doi.org/10.1002/jcb.10232
Abstract
The rapid synthesis of heat shock proteins (Hsps) in cells subjected to environmental challenge is controlled by heat shock transcription factor‐1 (Hsf1). Regulation of Hsps by Hsf1 is highly complex and, in the whole organism, remains largely unexplored. In this study, we have used mouse embryo fibroblasts and bone marrow progenitor cells from hsf1−/− mice as well as hsp70.3‐lacZ knock‐in mice bred on the hsf1deficient genetic background (hsf1−/−‐hsp70.3+/−‐lacZ), to further elucidate the function of Hsf1 and its participation as a transcriptional activator of Hsp70 synthesis under normal or heat‐induced stress conditions in vitro and in vivo. The results revealed that heat‐induced Hsp70 expression in mouse tissue is entirely controlled by Hsf1, whereas its activity is not required for tissue‐specific constitutive Hsp70 expression. We further demonstrate that Hsf1 is critical for maintaining cellular integrity after heat stress and that cells from hsf1−/− mice lack the ability to develop thermotolerance. This deficiency is explained by the elimination of stress‐inducible Hsp70 and Hsp25 response in the absence of Hsf1 activity, leading to a lack of Hsp‐mediated inhibition of apoptotic cell death via both caspase‐dependent and caspase‐independent pathways. The pivotal role of the Hsf1 transactivator in regulating rapid synthesis of Hsps as a critical cellular defense mechanism against environmental stress‐induced damage is underlined. J. Cell. Biochem. 86: 376–393, 2002.Keywords
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